Activated macrophages obtained from murine sarcoma virus (MSV)-induced tumors or from animals inoculated with other agents were found to nonspecifically suppress lymphokine production. Supression occurred very early during the culture period and was associated with a decrease in protein synthesis in the lymphocytes. Macrophage cell lines were shown to be functionally heterogeneous, with some cytolytic and cytostatic for tumor cells. Secondary T cell mediated cytotoxic responses to tumor associated antigens was induced by infectious virus. Long term T cell lines have been established in vitro from immune spleen cells some of which have become transformed to produce tumors when inoculated in vivo. Lysosomal extracts from MSV-induced tumors inhibited T cell-mediated cytotoxicity. Natural killer (NK) activity was found to be augmented by interferon and inhibited both in vitro and in vivo by prostaglandins. Heterogeneity of NK cells was demonstrated, with some expressing Thy 1 antigen (70-90% in nudes) and some having no detectable Thy 1 antigen.